title: Perineural invasion in extrahepatic cholangiocarcinoma: prognostic impact and treatment strategies.
abstract: BACKGROUND
  The significance of perineural invasion in extrahepatic cholangiocarcinoma has not been fully elucidated. This study aims to determine the prognostic impact of and optimal treatment strategy for perineural invasion in patients with extrahepatic cholangiocarcinoma.
  
  
  METHODS
  Medical records of 133 patients with extrahepatic cholangiocarcinoma who underwent curative resection were reviewed retrospectively. Ninety-eight patients had perineural invasion and 35 patients did not. Univariate and multivariate survival analyses were performed to clarify the prognostic impact of and optimal treatment strategy for perineural invasion.
  
  
  RESULTS
  Only tumor differentiation (P=0.024) was independently associated with perineural invasion in the multivariate logistic regression model. Multivariate survival analysis revealed that perineural invasion (P=0.002), resection margin status(P=0.016), and International Union Against Cancer (UICC) pT factor (P=0.015) were independent prognostic factors of overall survival. Overall 5-year survival rates for patients with and without perineural invasion were 28 and 74 %, respectively. Among 98 patients with perineural invasion, the use of adjuvant chemotherapy (P=0.003), lymph node status (P=0.015), resection margin status (P=0.008), and UICC pT factor (P=0.016) were independently associated with overall survival by multivariate analysis. Overall 5-year survival rates for patients with perineural invasion who did and did not receive adjuvant chemotherapy were 33 and 21 %, respectively (P=0.023).
  
  
  CONCLUSIONS
  Perineural invasion is a potent prognostic factor in extrahepatic cholangiocarcinoma. Adjuvant chemotherapy may improve the overall survival of patients with perineural invasion.
authors.affiliation: Department of Surgery, Institute of Biomedical and Health Sciences, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima 734-8551, Japan. mura777@hiroshima-u.ac.jp
authors.forename: Yoshiaki
authors.initials: Y
authors.lastname: Murakami
authors.forename: Kenichiro
authors.initials: K
authors.lastname: Uemura
authors.forename: Takeshi
authors.initials: T
authors.lastname: Sudo
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Hashimoto
authors.forename: Naru
authors.initials: N
authors.lastname: Kondo
authors.forename: Naoya
authors.initials: N
authors.lastname: Nakagawa
authors.forename: Takeshi
authors.initials: T
authors.lastname: Muto
authors.forename: Hayato
authors.initials: H
authors.lastname: Sasaki
authors.forename: Kazuhide
authors.initials: K
authors.lastname: Urabe
authors.forename: Taijiro
authors.initials: T
authors.lastname: Sueda
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D001650:Bile Duct Neoplasms / Q000188:drug therapy / Q000473:pathology* / Q000601:surgery; D017734:Bile Ducts, Extrahepatic; D017024:Chemotherapy, Adjuvant; D018281:Cholangiocarcinoma / Q000188:drug therapy / Q000556:secondary* / Q000601:surgery; D003841:Deoxycytidine / Q000008:administration & dosage / Q000031:analogs & derivatives; D004338:Drug Combinations; D005260:Female; D006498:Hepatectomy / Q000009:adverse effects; D006801:Humans; D053208:Kaplan-Meier Estimate; D008207:Lymphatic Metastasis; D008297:Male; D008875:Middle Aged; D060787:Neoplasm Grading; D009361:Neoplasm Invasiveness; D009367:Neoplasm Staging; D018365:Neoplasm, Residual; D010094:Oxonic Acid / Q000008:administration & dosage; D010525:Peripheral Nerves / Q000473:pathology*; D016016:Proportional Hazards Models; D012189:Retrospective Studies; D015996:Survival Rate; D005641:Tegafur / Q000008:administration & dosage; D016896:Treatment Outcome; D000093542:Gemcitabine
chemical_list: D004338:Drug Combinations; D003841:Deoxycytidine; C079198:S 1 (combination); D005641:Tegafur; D010094:Oxonic Acid; D000093542:Gemcitabine